MassIVE MSV000097115

Partial Public

Hypertrophic Cardiomyopathy-Associated CRYABR123W Activates Calcineurin, Reduces Calcium Sequestration, Alters the CRYAB Interactome and the Proteomic Response to Pathological Hypertrophy

Subscribe Comment Reanalyze Spectra Add Reanalysis

Description

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular condition in the world affecting around 1:500 people. HCM is characterized by ventricular wall thickening, decreased ventricular chamber volume and diastolic dysfunction. Inherited HCM is most commonly caused by sarcomere gene mutations, however approximately 50% of patients do not present with a known mutation highlighting the need for further research into additional pathologic mutations. CRYABR123W was previously identified as a novel sarcomere-independent mutation causing HCM associated with pathologic NFAT signaling in the setting of pressure overload. We generated stable H9C2 cell lines expressing FLAG tagged wild type and mutant CRYAB, which demonstrated that CRYABR123W has increased calcineurin activity. Using Alphafold to predict structural and interaction changes we generated a model where CRYABR123W uniquely binds to the autoinhibitory domain of calcineurin. Co-immunoprecipitation using the CRYAB FLAG tag fol-lowed by mass spectrometry showed novel and distinct changes in the protein interaction patterns of CRYABR123W. Finally, mouse hearts extracted from our wild type and CRYABR123W model with and without pressure overload caused by transverse aortic constriction (TAC) were used in global proteomic and phosphoproteomic mass spectrometry analysis which showed dysregulation in cytoskeletal, metabolomic, cardiac and immune function. Our data illustrates how CRYABR123W drives calcineurin activation and exhibits distinct changes in protein interaction and cellular pathways during the development of HCM and pathological cardiac hypertrophy. [doi:10.25345/C5FB4WZ76] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: CRYAB ; Alpha-B-Crystallin ; Hypertrophic Cardiomyopathy ; Transverse Aortic Constriction ; Mass Spectrometry ; DatasetType:Proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Michael T. Chin, Tufts Medical Center, USA
Submitting User: athorkelsson

Publications

Thorkelsson A, Chou C, Tripp A, Ali SA, Galper J, Chin MT.
Hypertrophic Cardiomyopathy-Associated CRYABR123W Activates Calcineurin, Reduces Calcium Sequestration, and Alters the CRYAB Interactome and the Proteomic Response to Pathological Hypertrophy.
Int. J. Mol. Sci. 2025, 26, 2383. https://doi.org/10.3390/ijms26062383.

Number of Files:
Total Size:
Spectra:
Subscribers:
 
Owner Reanalyses
Experimental Design
    Conditions:
    Biological Replicates:
    Technical Replicates:
 
Identification Results
    Proteins (Human, Remapped):
    Proteins (Reported):
    Peptides:
    Variant Peptides:
    PSMs:
 
Quantification Results
    Differential Proteins:
    Quantified Proteins:
 
Browse Dataset Files
 
FTP Download Link (click to copy):

Species

Instrument

Modifications

- Dataset Reanalyses

+ Dataset History

Click here to queue conversion of this dataset's submitted spectrum files to open formats (e.g. mzML). This process may take some time.

When complete, the converted files will be available in the "ccms_peak" subdirectory of the dataset's FTP space (accessible via the "FTP Download" link to the right).
Number of distinct conditions across all analyses (original submission and reanalyses) associated with this dataset.

Distinct condition labels are counted across all files submitted in the "Metadata" category having a "Condition" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct biological replicates across all analyses (original submission and reanalyses) associated with this dataset.

Distinct replicate labels are counted across all files submitted in the "Metadata" category having a "BioReplicate" or "Replicate" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct technical replicates across all analyses (original submission and reanalyses) associated with this dataset.

The technical replicate count is defined as the maximum number of times any one distinct combination of condition and biological replicate was analyzed across all files submitted in the "Metadata" category. In the case of fractionated experiments, only the first fraction is considered.

"N/A" means no results of this type were submitted.
Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

"N/A" means no results of this type were submitted.
Number of distinct protein accessions reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct unmodified peptide sequences reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

A protein is differentially abundant if its change in abundance across conditions is found to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated with statistical tests for differential abundance.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
This dataset may not contain all raw spectra data as originally deposited in PRIDE. It has been imported to MassIVE for reanalysis purposes, so its spectra data here may consist solely of processed peak lists suitable for reanalysis with most software.